According to the cholinergic hypothesis of memory impairment in Alzheimer's disease, senile dementia and age-associated memory impairment a deficiency of cholinergic function plays a major role in the progressive development of the disease. This has led to the belief that enhancement of muscarinic cholinergic transmissions at cerebal cortical sites would be beneficial for treatment of the disease. Arecoline, a piperidine derivative, and aceclidine, a quinuclidine derivative are both muscarinic agonists; however, they exhibit undesirable clinical effects and there is a need for derivatives with more desirable clinical profiles.
Spiro derivatives of quinuclidine and piperidine are known to have cholinergic properties. For example, European Patent Application 0311313 discloses spirofurane and spirotetrahydrothiophene derivatives of quinuclidine and piperidine. A spiroisoxazolidin-3-one derivative, 2-aza-1-oxaspiro[4,5]-decan-3-one is known [J. Chem. Soc., Perkin Trans. 2, (10), 1355(1989)] as a chemical intermediate but to the best of our knowledge is not known to have any cholinergic properties. De Amici et al [Europ. J. of Med. Chem. 24, 171-177(1989)] disclose isoxazolidin-3-one derivatives of muscarone with muscarinic activity.